Overview

The primary cilium is a dramatic example of spatial organization in the cell. Composed of more than a thousand proteins, this elaborate structure projects from the surface of most mammalian cells. Often only a few microns long, cilia are marvelously complex machines that play a central role in the efficient detection and interpretation of signals from the environment. Primary cilia coordinate multiple signaling pathways important for embryogenesis, organogenesis, and sensory function. Defects in cilia lead to human pathologies ranging from congenital anomalies to cystic disease and obesity. A major goal in modern cell biology is to understand how cilia function as signaling centers.

We use the hedgehog signaling pathway as an accessible model to decipher fundamental principles of ciliary signal transduction. We expect that insights gained in these studies will help elucidate the function of this mysterious organelle and open the doors to the development of cilia-targeted therapeutics.

We approach scientific problems by integrating bulk methods, such as biochemical reconstitution and protein purification, with single cell methods, such as microscopy using innovative optical and chemical probes.

Primary cilium: small but elaborate. The inset shows a typical
fibroblast in culture with a cilium ( ~5µM x 0.5µM). Proteins targeted to cilia are carried by transport complexes that move the proteins towards the tip of the cilium (red path) or backtowards the base of the cilium (green path) for exit.